Therapeutic agent (e.g. drug) delivery is an important aspect of medical treatment since the efficacy of a drug is directly related to its administration. Some therapies require repetitive drug administration to the patient over a long period of time, and in many cases long term consistent administration of drug is desirable. In addition, patient compliance with repetitive, long term drug administration can be an issue in some instances.
Considerable advances have been made in the field of drug delivery technology over the last three decades, resulting in many breakthroughs in clinical medicine. The creation of therapeutic agent delivery devices that are capable of delivering therapeutic agents in controlled ways still presents many challenges. One of the significant requirements for an implantable drug delivery device is controlled release of therapeutic agents, ranging from small drug molecules to larger biological molecules. In many instances, it is particularly desirable to achieve a continuous drug release profile whereby the concentration of drug in the bloodstream remains substantially constant throughout an extended delivery period. It can also be desirable for the implantable drug delivery device to provide continuous drug release via passive control mechanisms to minimize device complexity.
These devices have the potential to improve therapeutic efficacy, diminish life-threatening side effects, improve patient compliance, minimize the intervention of healthcare personnel, reduce the duration of hospital stays, and decrease the diversion and abuse of controlled substances.
By providing a more consistent release, it is possible to improve the therapeutic efficacy and simultaneously decrease the side effects (e.g. toxicity of temporary overdosing or diminished activity associated with a small drug concentration in the plasma) associated with multiple administrations of higher dosages.
The solubility of certain therapeutic agents can provide dosing and application challenges. For example, a therapeutic agent with poor water solubility requires a greater volume of solvent to dissolve the therapeutic agent in the injection or implantable delivery device in order to provide an effective dosing level for extended duration. In cases where it is desirable to have an extended dosing period, the volume of solvent and the dissolved therapeutic agent may be large, and therefore the implantable delivery device may be prohibitively large. Long term dosing of low solubility therapeutic agents in a small implantable delivery device is desirable.
In certain applications, implantable drug delivery devices may incorporate geometric constraints to provide for a controlled release rate of the therapeutic agent. For example, certain implantable drug delivery devices may utilize nanochannels to restrict the rate at which therapeutic molecules can diffuse from the device. In particular applications, geometric constraints can control the diffusion rate so that it is substantially independent of the concentration of the remaining therapeutic agent within the delivery device. These geometric constraints include nanochannels that are fabricated 2-5 times larger than the hydrodynamic size of the agent molecule. However, if the therapeutic molecule is sufficiently small, it can be difficult, if not impossible, to create a geometric constraint dimensioned to provide for a controlled release rate at a therapeutically-effective level. In addition, such small geometric constraints may lead to insufficient release of the agent.
The issues raised above are merely exemplary of the potential shortcomings of existing systems and are not intended to be an exhaustive listing of the issues addressed by embodiments of the present disclosure.